The prognosis of poorly differentiated lung adenocarcinoma (PDLA) is determined by many clinicopathological factors. The aim of this study is identifying prognostic factors and developing reliable nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) in patients with PDLA. Patient data from the Surveillance, Epidemiology and End Results (SEER) database was collected and analyzed. The SEER database was used to screen 1059 eligible patients as the study cohort. The whole cohort was randomly divided into a training cohort (n = 530) and a test cohort (n = 529). Cox proportional hazards analysis was used to identify variables and construct a nomogram based on the training cohort. C-index and calibration curves were performed to evaluate the performance of the model in the training cohort and test cohorts. For patients with PDLA, age at diagnosis, gender, tumor size were independent prognostic factors both for overall survival (OS) and cancer-specific survival (CSS), while race and number of nodes were specifically related to OS. The calibration curves presented excellent consistency between the actual and nomogram-predict survival probabilities in the training and test cohorts. The C-index values of the nomogram were 0.700 and 0.730 for OS and CSS, respectively. The novel nomogram provides new insights of the risk of each prognostic factor and can assist doctors in predicting the 1-year, 3-year and 5-year OS and CSS in patients with PDLA.

Introduction Surgery is one of the main approaches for the comprehensive treatment of early and locally advanced non-small cell lung cancer (NSCLC). This study conducts a nationwide multicentre study to explore factors that could influence the outcomes of patients with I–IIIA NSCLC who underwent curable surgery in real-world scenarios. Methods and analysis All patients diagnosed with NSCLC between January 2013 and December 2020 will be identified from 30 large public medical services centres in mainland China. The algorithm of natural language processing and artificial intelligence techniques were used to extract data from electronic health records of enrolled patients who fulfil the inclusion criteria. Six categories of parameters are collected and stored from the electronic records, then the parameters will be structured as a high-quality structured case report form. The code book will be compiled and each parameter will be classified and designated a code. In addition, the study retrieves the survival status and causes of death of patients from the Chinese Centre for Disease Control and Prevention. The primary endpoints are overall survival and the secondary endpoint is disease-free survival. Finally, an online platform is formed for data queries and the original records will be stored as secure electronic documents. Ethics and dissemination The study has been approved by the Ethical Committee of the Chinese Academy of Medical Sciences. Study findings will be disseminated via presentations at conferences and publications in open-access journals. This study has been registered in the Chinese Trial Register (ChiCTR2100052773) on 11 May 2021, http://www.chictr.org.cn/showproj.aspx?proj=136659. Trial registration number ChiCTR2100052773.

Lipid metabolism is a key factor in tumorigenesis and drug resistance, and models related to lipid metabolism have shown potential to predict survival and curative effects of adjuvant therapy in various cancers. However, the relationship between lipid metabolism and prognosis and treatment response of lung adenocarcinoma (LUAD) are still unclear. We enrolled seven bulk RNA-sequence datasets (GSE37745, GSE19188, GSE30219, GSE31547, GSE41271, GSE42127, and GSE72094) from the GEO database and one single-cell RNA-sequencing dataset (GSE117570) from the TISCH2 database. Non-negative matrix factorization (NMF) was utilized to construct the risk score model based on lipid score calculated by GSVA algorithm. Phs000452.v3, PMID: 26359337, PMID: 32472114, PRJEB23709 datasets were used to test the response to immunotherapy. Drug sensitivity analysis was assessed according to the GDSC database, and immunotherapy response was evaluated using the Wilcoxon test. Cellular function assays including clone formation, EDU assays and flow cytometry were implemented to explore the phenotype alteration caused by the knockdown of PTDSS1, which is one of key gene in risk score model. We analyzed both bulk and single-cell RNA sequencing data to establish and validate a risk score model based on 18 lipid metabolism-related genes with significant impact on prognosis. After divided the patients into two groups according to risk score, we identified differences in lipid-related metabolic processes and a detailed portrait of the immune landscapes of high- and low-risk groups. Moreover, we investigated the potentials of our risk score in predicting response to immunotherapy and drug sensitivity. In addition, we silenced PTDSS1 in LUAD cell lines, and found that the proliferation of the cells was weakened, and the apoptosis of the cells was increased. Our study highlights the crucial roles of lipid metabolism in LUAD and provides a reliable risk score model, which can aid in predicting prognosis and response to immunotherapy. Furthermore, we investigated the roles of PTDSS1 in LUAD carcinogenesis, which showed that PTDSS1 regulated proliferation and apoptosis of LUAD cells.

AbstractCholesterol disorder has been implicated in the progression of lung cancer, the mechanism of which remains largely unknown. In this study, we evidenced that cholesterol promoted the proliferation, migration and invasion of lung adenocarcinoma cells (LAC) in vitro, and enhanced LAC metastasis in vivo. Further investigation demonstrated that cholesterol treatment induced the expression of MYADM. Cholesterol-induced interaction between MYADM and Rac1 triggered AKT phosphorylation and c-Myc expression. c-Myc positively regulated the transcriptions of MCT1 and MYADM. MYADM knockdown notably inhibited the expression of Rac1, phosphorylated AKT, c-Myc and MCT1 despite in the presence of cholesterol. Blocking AKT phosphorylation restrained cholesterol-induced the expression of MYADM, Rac1 and c-Myc while AKT activation elevated the levels of MYADM, Rac1 and c-Myc. In addition, MYADM knockdown promoted E-Cadherin expression, and inhibited the expression of β-Catenin, MMP2, MMP9 and vimentin. As expected, inhibiting MYADM significantly attenuated cholesterol-induced proliferation, migration and invasion of LAC in vitro, and reduced high cholesterol diet-induced LAC metastasis in vivo. Intriguingly, MYADM knockdown remarkably decreased the levels of lactate in serum and tumors, confirming the positive regulator of MYADM in MCT1 expression. These results suggested that cholesterol should induce the proliferation and metastasis of LAC by regulating MYADM/Rac1/AKT/c-Myc/MCT1 axis.

Chemotherapy resistance and treatment failure hinder clinical cancer treatment. Src, the first mammalian proto-oncogene to be discovered, is a valuable anti-cancer therapeutic target. Although several c-Src inhibitors have reached the clinical stage, drug resistance remains a challenge during treatment. Herein, a positive feedback loop between a previously uncharacterized long non-coding RNA (lncRNA), which the authors renamed lncRNA-inducing c-Src tumor-promoting function (LIST), and c-Src is uncovered. LIST directly binds to and regulates the Y530 phosphorylation activity of c-Src. As a c-Src agonist, LIST promotes tumor chemoresistance and progression in vitro and in vivo in multiple cancer types. c-Src can positively regulate LIST transcription by activating the NF-κB signaling pathway and then recruiting the P65 transcription factor to the LIST promoter. Interestingly, the LIST/c-Src interaction is associated with evolutionary new variations of c-Src. It is proposed that the human-specific LIST/c-Src axis renders an extra layer of control over c-Src activity. Additionally, the LIST/c-Src axis is of high physiological relevance in cancer and may be a valuable prognostic biomarker and potential therapeutic target.

Purpose Mitophagy and aging (MiAg) are very important pathophysiological mechanisms contributing to tumorigenesis. MiAg-related genes have prognostic value in lung adenocarcinoma (LUAD). However, prognostic, and immune correlation studies of MiAg-related genes in LUAD are lacking. Methods MiAg differentially expressed genes (DEGs) in LUAD were obtained from public sequencing datasets. A prognostic model including MiAg DEGs was constructed according to patients divided into low- and high-risk groups. Gene Ontology, gene set enrichment analysis, gene set variation analysis, CIBERSORT immune infiltration analysis, and clinical characteristic correlation analyses were performed for functional annotation and correlation of MiAgs with prognosis in patients with LUAD. Results Seven MiAg DEGs of LUAD were identified: CAV1 , DSG2 , DSP , MYH11 , NME1 , PAICS , PLOD2 , and the expression levels of these genes were significantly correlated ( P < 0.05). The RiskScore of the MiAg DEG prognostic model demonstrated high predictive ability of overall survival of patients diagnosed with LUAD. Patients with high and low MiAg phenotypic scores exhibited significant differences in the infiltration levels of eight types of immune cells ( P < 0.05). The multi-factor DEG regression model showed higher efficacy in predicting 5-year survival than 3- and 1-year survival of patients with LUAD. Conclusions Seven MiAg-related genes were identified to be significantly associated with the prognosis of patients diagnosed with LUAD. Moreover, the identified MiAg DEGs might affect the immunotherapy strategy of patients with LUAD.

[Objectives] By studying the plasma metabolomics of patients with different pulmonary nodules and healthy people, we can find the difference in plasma low-molecular metabolites among them. [Methods] Patients with pulmonary nodules admitted to our department were divided into three groups: pulmonary metastatic carcinoma (PMC), benign pulmonary nodules (BPN), and primary lung cancer (PLC). Meanwhile healthy people were enrolled as healthy population group (HPG). PLC and HPG were equally divided into the Discovery Set and Validation set. [Results] Five significant low-molecular metabolites were found by comparison of four groups as a whole. Four to six metabolites were selected by comparison of the three pulmonary nodule groups with healthy people respectively. The AUC of ROC of these metabolites were all＞0.93. Each pairwise comparison within the three pulmonary nodule groups all found three metabolites, whose AUC of ROC were all＞0.83. From the comparison of PLC and HPG in the discovery set, six metabolites were selected. Their AUC of ROC were all greater than 0.95 in the validation set, indicating that they had a strong ability to differentiate between primary lung cancer and healthy people. [Conclusions] We can find the significant changes of some low-molecular metabolites among three pulmonary nodules and healthy people. These metabolites had the potential to be biomarkers for screening and differential diagnosis of lung cancer.

Chylothorax is a rare and challenging complication of thoracic surgery. Whereas most current studies focus on postoperative treatment and preventative measures for esophageal cancer surgery, the current study investigates the impact of prophylactic ligation of the thoracic duct branch on postoperative chylothorax after pulmonary resection for right lung cancer. The subjects of this retrospective study were 1165 patients who underwent right pulmonary resection and mediastinal lymph-node dissection in our department between January 2015 and August 2019. Those who underwent prophylactic ligation of the thoracic duct branch after 4R lymph-node dissection were assigned to group A (n = 475), and those who did not were assigned to group B (n = 690). The incidence of postoperative chylothorax, the success rate of conservative treatment, the postoperative hospital stay, and the chest drainage volume were recorded and compared statistically between the two groups. The incidence of postoperative chylothorax was significantly lower in group A than in group B (0.84% vs. 2.90%, p = 0.015). Patients who had a chylothorax in group A had a significantly shorter postoperative hospital stay, less mean drainage volume per day, and less total drainage than those in group B (7.25 ± 0.50 days vs. 11.00 ± 2.81 days, p = 0.003; 0.64 ± 0.04 L vs. 0.80 ± 0.09 L, p = 0.003; 4.64 ± 0.40 L vs. 8.82 ± 2.84 L; p = 0.002). The success rate of conservative treatment was higher in group A than in group B, but the difference was not significant (100% vs. 75.0%, p = 0.544). Performing prophylactic ligation of the thoracic duct branch during right pulmonary resection and mediastinal lymph-node dissection is an effective and safe method of preventing postoperative chylothorax.

Long noncoding RNAs (lncRNAs) have emerged as regulators of gene expression and play critical regulatory roles in diverse biological functions and diseases, including cancer. In this study, we report the downregulation of LINC01089 in non-small cell lung cancer (NSCLC) samples, relative to adjacent non-tumor tissues, and demonstrate its role in the inhibition of proliferation, migration, and epithelial–mesenchymal transition (EMT) of NSCLC cells. Mechanistic analysis indicates that LINC01089 acts as a sponge for miR-27a, regulating its expression in NSCLC. Interestingly, LINC01089 mediated the upregulation of SFRP1 expression by inhibiting the Wnt/β-catenin–EMT pathway and inhibiting the epithelial–mesenchymal transition of NSCLC via sponging miR-27a. Overall, our findings highlight LINC01089’s tumorigenic role and regulatory mechanism in NSCLC, thereby suggesting its potential as a therapeutic target for managing NSCLC.

Objective: To explore the safety and therapeutic effect of programmed death 1 (PD-1) antibody combined with chemotherapy as a neoadjuvant therapy for patients with stage Ⅱ to Ⅲ non-small cell lung cancer (NSCLC). Methods: Thirteen patients, who had been diagnosed as stage Ⅱ-Ⅲ NSCLC and received PD-1 inhibitor plus chemotherapy as a neoadjuvant treatment in National Cancer Center/Cancer Hospital were recruited. The patients received consecutive neoadjuvant chemotherapy for 21 days as a cycle and the therapeutic efficacy was evaluated after two cycles. Results: At the last time of follow-up on December 2, 2019, the objective response rate (ORR) and disease control rate (DCR) of these patients were 61.5% (95% CI 30.9%-92.1%) and 100%, respectively. The downregulation rate of disease stage was 61.5% (8/13). The resectable rate was 38.5% (5/13), among them, the major pathologic response (MPR) was 60.0% (3/5) and the complete pathologic response (CPR) was 20.0% (1/5). The neoadjuvant chemotherapy displayed a low incidence of adverse reaction. The main grade 3 to 4 toxicities were neutropenia (38.5%) and leukopenia (23.1%). There was no significant immune-related toxicity. The safety and tolerability of perioperative period of patients underwent resection were promising. Conclusions: Immunotherapy combined with chemotherapy as a neoadjuvant treatment is an effective, low-toxicity treatment manner, which has perioperative safety and high rate of MPR for patients with resectable NSCLC. It is a promising treatment option for patients with stage Ⅱ to Ⅲ NSCLC.

肺是恶性肿瘤转移的第二好发部位,肺转移瘤切除术(PM)已成为胸外科的常见手术.研究认为肺转移瘤切除术可以使部分患者获益,目前关于肺转移瘤切除术的手术适应证、手术方式、淋巴结处理及预后影响因素等方面仍存在争议.全文从上述方面对肺转移瘤的手术治疗作一论述.

Objective: To investigate the rule of mediastinal lymph node metastasis of papillary thyroid carcinoma and the application of therapeutic mediastinal lymph node dissection through the sternotomy approach in the treatment of mediastinal lymph node metastasis of papillary thyroid carcinoma. Methods: All cases of papillary thyroid carcinoma with mediastinal lymph node metastasis treated through sternotomy cooperated by thoracic surgeons and head and neck surgeons from January 2006 to January 2017 in Cancer Hospital of Chinese Academy of Medical Sciences were included in this study. The distribution, metastasis rate, metastasis degree, surgical method, surgical complications and postoperative survival of patients with mediastinal lymph node metastasis were retrospectively analyzed. Results: A total of 31 patients (16 males and 15 females) with papillary thyroid cancer with mediastinal lymph node metastasis, with a median age of 46 (19-65) years, were enrolled in the group. Partial upper sternotomy was used in 28 cases, and total sternotomy was used in 3 cases. The mediastinal lymph nodes of papillary thyroid carcinoma metastasized farthest to the station 6, and the lymph node metastasis rate of each group from high to low was: 2R (61%), 1R (39%), 3A (39%), 1L (16%), 2L (10%), 4R (10%), 5 (3%) and 6 (3%). No metastasis was observed in station 3P, 4L and 7. In addition, the degree of lymph node metastasis at station 2R was the highest, reaching 35% (77/219). Extra-nodal invasion of mediastinal metastatic lymph nodes in thyroid papillary carcinoma is common (23%), easily fuses into masses (23%) and invades peripheral vascular nerves (26%). Up to 29% of blood transfusions are required during or after surgery due to oozing or bleeding (9/31). The 1-, 3-, 5-and 10-year survival rates of patients undergoing surgical treatment were 94%, 94%, 87% and 81%, respectively. Conclusion: Papillary thyroid carcinoma can metastasize to almost all mediastinal lymph nodes except station 3P, 4L and 7. Radical mediastinal lymph node dissection through sternotomy is an effective method for the treatment of mediastinal lymph node metastasis of thyroid papillary carcinoma.

Objective Through the summary and analysis of large samples, the characteristic imaging manifestations of intrapulmonary lymph nodes (IPLNs) were quantified, and two corresponding rating tables were developed. These rating tables could be used to distinguish the IPLNs from primary lung cancer, so as to improve the diagnostic accuracy and help clinicians make correct judgments and decisions. Methods A total of 82 patients with 110 IPLNs and 35 patients with primary lung cancer lesions were collected from June 2017 to December 2018. All lesions were solid nodules of less than 12mm in diameter, which were confirmed by pathology. Observation indicators included location, size, shape, density, border and internal vacuoles of nodules, linear high-density shadow around the nodules, distance from the pleura, pleural indentation, and so on. Results There were statistically significant differences in the location, size, shape, internal vacuole of the nodules, and distance from the pleura ( p <0.05). The diagnostic scoring table of the nature of solid nodules and the malignant risk table were drawn. The nodule corresponding to Level A was most likely the primary lung cancer, and surgical resection was recommended. The nodule corresponding to Level C was most likely IPLNs, and it was better to receive no treatment currently. The positive predictive value was 81% (23/28), the negative predictive value was 97% (89/92), the sensitivity was 63% (23/35), and the specificity was 81% (89/110). Conclusion For the pulmonary solid nodules of less than 12mm in diameter and unknown nature, the evaluation in accordance with the Score Table and the Risk Level Table of this study can be more accurate and faster than the original judgment, which will help clinicians in diagnosis and treatment decisions.

The National Comprehensive Cancer Network (NCCN) clinical practice guideline of non-small cell lung cancer (NSCLC) in 2018 points out that anatomic pulmonary resection is a preferred option for early stage NSCLC. With the development of video-assisted thoracoscopy, minimally invasive thoracic surgery represented by thoracoscopy has been widely used in clinical practice. Video-assisted thoracoscopic segmentectomy has become one of the treatment options for early stage NSCLC. Clinical studies have found that sublobar resection can achieve similar results and preserve more pulmonary function in the treatment of early stage NSCLC compared with lobectomy, but the changes of pulmonary function after segmentectomy are still controversial. This article focuses on the research progress of pulmonary function changes in NSCLC patients after video-assisted thoracoscopic segmentectomy.

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (P<0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% (P<0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P<0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% (P<0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% (P<0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS (P<0.05 for all). Conclusions: The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

目的:通过整合肺腺癌(lung adenocarcinoma,LUAD)临床信息组、基因组和转录组的多组学信息,构建预后相关风险预测模型,为肺腺癌患者的预后风险预测提供依据.方法:通过肿瘤基因图谱(the cancer genome atlas,TCGA)网站下载522例肺腺癌患者数据,完成肺腺癌患者多组学数据库构建.对经过质量控制的数据库,采用Cox比例风险模型评价多组学数据对LUAD预后的影响,构建基于临床信息、基因分型和基因表达多组学信息的预后风险预测模型,并使用受试者工作特征(receiver operating characteristic,ROC)曲线和曲线下面积(area under curve,AUC)评估预后模型风险识别的能力.结果:共386例肺腺癌患者纳入多组学数据库,分别筛选出1个临床信息组、5个基因组单核苷酸多态性(single nucleotide polymorphisms,SNP)和4个转录组mRNA预后相关特征因素与肺腺癌的预后相关.与肺腺癌低风险组相比,高风险组患者较低风险组的预后更差(HR=3.67,95％CI=2.46～5.49,P=1.96×10-10),联合基因组、转录组与临床信息构建多组学预后指数后,其ROC曲线下面积为0.694(95％CI=0.633～0.754).结论:采用联合临床信息组、基因组和转录组特征的多组学信息构建的预后风险预测指数可有效区分肺腺癌患者预后好坏,其研究结果将为肺腺癌患者的精准治疗提供有效支撑.

Objective The objective of this study was to explore the association between human papillomavirus( HPV) and prognosis of lung cancer by meta-analysis. Methods The PubMed,Embase and Cochrane literature databases studies were searched using a combination of subject terms and free words. As of October 2018,a total of 123 related documents were obtained. After screen-ing the literature according to inclusion and exclusion criteria,the basic information of the study,HPV detection methods,lung cancer patients,hazard ratio(HR)values and 95% confidence interval(CI)were extracted from each study. The meta-analysis of random effects models was used to evaluate the correlation between HPV infection and prognosis in patients with lung cancer. Heterogeneity was assessed using the Q test and I2statistics,and publication bias was tested using Egger′s linear regression test and Begg′s rank cor-relation test. Results The study finally included 11 articles(9 in Asia,2 in Europe and US),and 1439 patients with lung cancer. Meta-analysis using a random-effects model showed no significant association between HPV infection and prognosis of lung cancer (HR=0. 90,95% CI:0. 71~1. 13). A stratified analysis of lung cancer pathological subtypes showed that the prognosis of patients with HPV-infected lung adenocarcinoma was significantly better than that in patients without HPV-infected lung adenocarcinoma (HR=0. 65,95% CI:0. 49~0. 85). Sensitivity analysis was performed by sequentially removing the included studies,and the results were not statistically significant. The results of Egger′s test(P=0. 708)and Begg′s test(P=0. 784)suggest that there is no publica-tion bias in this study. Conclusion HPV infection may be related to the prognostic of patients with lung adenocarcinoma. More basic and clinical studies are needed to further explore the association between HPV infection and lung adenocarcinoma as well as the corre-sponding mechanisms in the future.

食管胃交界部腺癌(adenocarcinoma of esopha-gogastric junction,EGJ)在国内传统上常常称为贲门癌.因其解剖位置的特殊性,虽然在肿瘤的命名、手术入路、消化道重建方式及淋巴结清扫范围等方面达成了诸多共识,但一直以来也存在较多争议.我们通过分析各学会最新的指南与分期系统,结合最新文献,探讨目前 EGJ外科治疗中的争议与共识.

Background and objective Surgeons are the direct decision-makers and performers in the surgical treatment of patients with lung cancer. Whether the differences among doctors affect the survival of patients is unclear. This study analyzed the five-year survival rates of different thoracic surgeries in patients undergoing surgery to assess the physician's impact and impact. Methods A retrospective analysis of five years between 2002-2007 in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sci-ences, for surgical treatment of lung cancer patients. According to different surgeons grouping doctors to com-pare the basic information of patients, surgical methods, short-term results and long-term survival differences. Results A total of 712 patients treated by 11 experienced thoracic surgeons were included in this study. The patients have nosignificant difference with gender, age, smoking, pathological type between groups. There were significant differences in clinical staging, surgery type, operation time, blood transfusion rate, number of lymph node dissection, palliative resection rate, postoperative complications and perioperative mortality. There was a significant difference in five-year survival rates among patients treated by different doctors. This difference can be seen in all clinical stage analyzes with consistency. In the multivariate analysis, it was suggested that surgeon was an independent factor influencing the prognosis of patients. Conclusion Thoracic surgeon has a significant effect on the therapeutic effect of lung cancer patients.